NCT02090413

Brief Summary

The primary objective of the study is to evaluate whether 150 mg enteric-coated aspirin (acetylsalicylic acid \[ASA\]) taken twice a day (BID) with dimethyl fumarate (DMF) administration or 75 mg enteric-coated ASA taken once daily in the morning (QAM) with DMF administration reduces the incidence and/or severity of flushing events in subjects with relapsing-remitting multiple sclerosis (RRMS) compared with ASA-placebo administered with DMF in the clinical practice setting. Secondary objectives of this study are: to evaluate the safety and tolerability of DMF administered with and without enteric-coated ASA in the clinical practice setting; to evaluate the impact of DMF administration on quality of life as measured by the Short Form 36 (SF-36®) and European Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L) questionnaires.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
241

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2014

Geographic Reach
2 countries

21 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 18, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

May 1, 2014

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2015

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2015

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 28, 2016

Completed
Last Updated

December 28, 2016

Status Verified

November 1, 2016

Enrollment Period

9 months

First QC Date

March 14, 2014

Results QC Date

November 1, 2016

Last Update Submit

November 1, 2016

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

multiple sclerosisflushingaspirin

Outcome Measures

Primary Outcomes (4)

  • Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Global Flushing Severity Scale (MGFSS)

    Participant-reported flushing events during the first 4 weeks treatment, recorded on the hand-held participant reporting device (eDiary) as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.

    Day 2 to Week 4

  • Percentage of Participants Reporting Overall Flushing Events During the First 4 Weeks of Treatment, as Assessed by the Modified Flushing Severity Scale (MFSS)

    Participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin. This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).

    Day 1 to Week 4

  • Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MGFSS

    Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MGFSS. The MGFSS measures the side effects related to flushing during the past 24 hours. Flushing means redness, warmth, tingling or itching of the skin. Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects). Day 1 data are not included in the analysis because MGFSS question refers to last 24 hours flushing score.

    Day 2 to Week 4

  • Worst Severity Scores of Overall Flushing During the First 4 Weeks of Treatment, as Assessed by MFSS

    Worst severity of participant-reported flushing events during the first 4 weeks of treatment recorded on the eDiary as assessed by MFSS. MFSS questionnaire measures the side effects related to flushing following drug administration. Flushing means redness, warmth, tingling or itching of the skin.This questionnaire relates only to the period of time since the investigational drug was administered and was to be completed within 10 hours of taking the study drug (2 times/day). Each question is rated on a scale from 0 (no flushing side effects) to 10 (extreme flushing side effects).

    Day 1 to Week 4

Secondary Outcomes (19)

  • Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MGFSS

    Week 5 to Week 12

  • Percentage of Participants Reporting Overall Flushing Events During Weeks 5-8 and Weeks 9-12 of Treatment, as Assessed by MFSS

    Week 5 to Week 12

  • Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MGFSS

    Week 5 to Week 12

  • Worst Severity Scores of Overall Flushing During Weeks 5-8 and Weeks 9-12 of the Study, as Assessed by MFSS

    Week 5 to Week 12

  • Duration of Flushing Episodes During Weeks 1-4, 5-8 and 9-12 of the Study, as Assessed by MGFSS

    Day 1 to Week 12

  • +14 more secondary outcomes

Study Arms (3)

DMF + ASA 150 mg BID

EXPERIMENTAL

DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 150 mg is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)

Drug: dimethyl fumarateDrug: acetylsalicylic acid

DMF + ASA 75 mg QAM

EXPERIMENTAL

DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA 75 mg is taken in the morning (QAM) and ASA-Placebo is taken in the evening (QPM) from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)

Drug: dimethyl fumarateDrug: acetylsalicylic acidDrug: ASA-Placebo

DMF + ASA-Placebo BID

EXPERIMENTAL

DMF 120 mg taken BID for the first 7 days and 240 mg BID from Week 2 through Week 48. ASA-Placebo is taken BID from Day 1 through Week 4. (Between Weeks 5 and 8, ASA is prohibited; between Weeks 9 and 48, ASA is allowed as needed.)

Drug: dimethyl fumarateDrug: ASA-Placebo

Interventions

dimethyl fumarateDRUG
Also known as: BG00012, Tecfidera, DMF
DMF + ASA 150 mg BIDDMF + ASA 75 mg QAMDMF + ASA-Placebo BID
acetylsalicylic acidDRUG

enteric-coated capsule

Also known as: ASA, aspirin
DMF + ASA 150 mg BIDDMF + ASA 75 mg QAM
ASA-PlaceboDRUG

matched placebo

Also known as: placebo
DMF + ASA 75 mg QAMDMF + ASA-Placebo BID

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Naïve to fumaric acid esters (e.g. DMF, Fumaderm, compounded fumarates)
  • Diagnosed with RRMS and satisfies the approved therapeutic indication for DMF
  • Participants of childbearing potential must practice effective contraception and be willing and able to continue contraception throughout the study
  • Ability to complete the tolerability scales accurately using the electronic diary (eDiary) and ability to complete the paper Flushing Diaries

You may not qualify if:

  • Inability or unwillingness to comply with study requirements or, at the discretion of the Investigator, is deemed unsuitable for study participation
  • One or more major comorbidities that, in the opinion of the Investigator, may affect the outcome of the study or otherwise makes the subject an unsuitable candidate for study participation. The prevailing product labels for both DMF and ASA should be used as guides
  • Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible)
  • Chronic use (≥7 consecutive days) of ASA- or nonsteroidal anti-inflammatory drugs (NSAID)-containing products within the month prior to enrollment in the study
  • A known intolerance to ASA
  • Active peptic ulceration or a history of peptic ulceration, hemophilia or other clotting disorders, or gout
  • Known hypersensitivity reactions (e.g., bronchospasm, rhinitis, urticaria) in response to ASA or NSAID administration
  • Impaired hepatic or renal function, in the opinion of the investigator
  • Female subject is pregnant, lactating, or will be attempting to become pregnant during the Double-Blind Period (first 12 weeks) of the study
  • Currently participating in another interventional clinical trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Research Site

Cork, Ireland

Location

Research Site

Dublin, Dublin 4, Ireland

Location

Research Site

Dublin, Dublin 7, Ireland

Location

Research Site

Dublin, Dublin 9, Ireland

Location

Research Site

Basingstoke, RG24 9NA, United Kingdom

Location

Research Site

Birmingham, B15 2TH, United Kingdom

Location

Research Site

Cardiff, CF14 4XW, United Kingdom

Location

Research Site

Edinburgh, EHA 2XU, United Kingdom

Location

Research Site

Exeter, EX2 5DW, United Kingdom

Location

Research Site

Glasgow, G51 4TH, United Kingdom

Location

Research Site

Leicester, LE5 4PW, United Kingdom

Location

Research Site

Liverpool, L9 7LJ, United Kingdom

Location

Research Site

London, SE5 9RS, United Kingdom

Location

Research Site

London, SW17 0QT, United Kingdom

Location

Research Site

London, WC1N 3BG, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Research Site

Norwich, NR4 7UY, United Kingdom

Location

Research Site

Nottingham, NG7 2UH, United Kingdom

Location

Research Site

Plymouth, PL6 8BX, United Kingdom

Location

Research Site

Salford, M6 8HD, United Kingdom

Location

Research Site

Swansea, SA6 6NL, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-RemittingMultiple SclerosisFlushing

Interventions

Dimethyl FumarateAspirin

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesSkin ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

FumaratesDicarboxylic AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsSalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Results Point of Contact

Title
Biogen Study Medical Director
Organization
Biogen
clinicaltrials@biogen.com

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2014

First Posted

March 18, 2014

Study Start

May 1, 2014

Primary Completion

February 1, 2015

Study Completion

November 1, 2015

Last Updated

December 28, 2016

Results First Posted

December 28, 2016

Record last verified: 2016-11

Locations

GB(17)IE(4)